Is WHO International Standard for Anti-SARS-CoV-2 Immunoglobulin Clinically Useful?

  1. Krzysztof Lukaszuk
  2. Jolanta Kiewisz
  3. Karolina Rozanska
  4. Amira Podolak
  5. Grzegorz Jakiel
  6. Izabela Woclawek-Potocka
  7. Lukasz Rabalski
  8. Aron Lukaszuk

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Abstract

Background

The introduction of vaccination against SARS-CoV-2 infection needs precise instruments for quality control of vaccination procedure, detection of poor immunological response and estimation of the achieved protection against the disease but also against infection and being infective.

Objective

To compare new automated SARS-CoV 2 Ig assay performance characteristics from the automated Elecsys SARS-CoV-2 S (Roche) with the new LIAISON® SARS-CoV-2 TrimericS IgG (DiaSorin) assay and their compatibility with WHO International Standard for anti-SARS-CoV-2 immunoglobulin. In the context of the mass vaccination programs, we undertook the investigation of clinical utility of the two new automated assays by analyzing results in samples collected at specified time points relative to the vaccination time.

Design

Prospective assay evaluation.

Patients

Medical staff undergoing vaccination with BioNTech/Pfizer Comirnaty vaccine between January and March 2021 (n = 79) and referred for serum antiSARS-CoV 2 Ig testing prior to vaccination, 21 days after the first dose, and 8, 14 and 30 days after the second dose. Main Outcome Measure(s): Serum antibody levels measured with Roche and DiaSorin assays.

Results

Intra-assay imprecision was low with DiaSorin at 3.46%; and Roche at 2.5%. The Passing-Bablok regression equation for all tested samples was y (DiaSorin) = 184.61 + (1.03 x Roche) and the correlation between the assays (r=0.587; p < 0.0001).

Conclusions

The novel automated assays exhibit strong concordance in calibration, with assay-specific interpretation required for routine clinical use. These results highlight the need for further work on the international standard of measurement of SARS-CoV 2 Ig especially in era of vaccination. The serological assays can be useful to detect IgG/IgM antibodies, to assess the degree of immunization, to trace the contacts, and to support the decision to readmit people to work or vaccinate them again. However, the values generated by both assays can be markedly different, and assay-specific and personalized interpretation is required.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.04.29.21256246: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: Ethical policy: The ethical approval was received from the Ethics Committee at the Gdansk Regional Medical Board (No KB - 4/21).
    Consent: All participants gave written informed consent for providing blood samples.
    Sex as a biological variablenot detected.
    RandomizationParticipants: Study included 79 randomly selected participants who underwent SARS-CoV-2 vaccination between Jan. 4, 2021 and Mar. 11, 2021.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationAuthentication: Both tests were validated against the WHO International Standard for anti-SARS-CoV-2 immunoglobulin.

    Table 2: Resources

    Antibodies
    SentencesResources
    The Roche assay detects antibodies (IgG) to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD) in human serum and plasma.
    S) protein receptor binding domain (RBD
    suggested: None
    When the upper estimating range was acquired, serum samples were diluted automatically (limited to 10x) using the reagents supplied by the manufacturer (Roche), or manually (no need for dilution more than 10x) with antibody-free serum (DiaSorin) and analyzed again.
    analyzed again.
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Strengths and limitations of the study require consideration. This study represents a pragmatic comparison of Ig measurement methods using an unselected group of patients referred for clinical Ig measurement before, during and after vaccination. The results still need some independent neutralization antibody measurements tests to be performed for their validation.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.04.29.21256246 on medRxiv